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Positive shifts of the GABAA receptor reversal potential due to altered chloride homeostasis is widespread after status epilepticus

  1. Gleb Barmashenko1,
  2. Stefan Hefft2,
  3. Ad Aertsen3,
  4. Timo Kirschstein1 and
  5. Rüdiger Köhling1

Article first published online: 7 SEP 2011

DOI: 10.1111/j.1528-1167.2011.03247.x

Issue

Epilepsia

Epilepsia

Volume 52, Issue 9, pages 1570–1578, September 2011


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How to CiteAuthor InformationPublication History

How to Cite

Barmashenko, G., Hefft, S., Aertsen, A., Kirschstein, T. and Köhling, R. (2011), Positive shifts of the GABAA receptor reversal potential due to altered chloride homeostasis is widespread after status epilepticus. Epilepsia, 52: 1570–1578. doi: 10.1111/j.1528-1167.2011.03247.x

Author Information

  1. 1

    Oscar Langendorff Institute of Physiology, University of Rostock, Rostock, Germany

  2. 2

    Neurocenter, University Hospital Freiburg, Freiburg, Germany

  3. 3

    Bernstein Center Freiburg, University of Freiburg, Freiburg, Germany

*Address correspondence to Timo Kirschstein, Oscar Langendorff Institute of Physiology, University of Rostock, 18057 Rostock, Germany. E-mail: timo.kirschstein@uni-rostock.de

Publication History

  1. Issue published online: 7 SEP 2011
  2. Article first published online: 7 SEP 2011
  3. Accepted July 12, 2011.
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Keywords:

  • Epilepsy;
  • GABA;
  • Gramicidin perforated patch-clamp;
  • NKCC1;
  • KCC2

Summary

Purpose:  γ-Aminobutyric acid (GABA)ergic transmission plays an important role in the initiation of epileptic activity and the generation of ictal discharges. The functional alterations in the epileptiform hippocampus critically depend on GABAergic mechanisms and cation-chloride cotransporters.

Methods:  To understand the cellular basis of specific functional alterations in the epileptic hippocampus, we studied physiologic characteristics and pharmacologically isolated evoked GABAA receptor–mediated inhibitory postsynaptic currents (IPSCs) recorded from principal neurons in hippocampal slices from status epilepticus (SE) and control rats using whole-cell and gramicidin perforated patch-clamp recordings.

Key Findings:  Whereas the resting membrane potential and input resistance were not significantly different between control and epileptic tissue, the reversal potential (EGABA) of IPSCs was significantly shifted to more positive values in SE rats with regard to the resting membrane potential. Pharmacologic experiments and quantitative reverse transcriptase polymerase chain reaction (RT-PCR) showed that the observed changes in the epileptic tissue were due to a decreased ratio of the main Cl− extrusion transporter (K+-Cl− cotransporter, KCC2) to the main Cl− uptake transporter (Na+-K+-2Cl− cotransporter, NKCC1).

Significance:  Our results suggest that alterations of cation-chloride cotransporter functions, comprising a higher NKCC1 action, contribute to hyperexcitability within the hippocampus following SE.

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